Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM

Laborértékek

• Any of the following criteria will exclude potential participants from the trial:
  • Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
  • History of intolerance or medical contraindication to beta blocker therapy
  • Resting Systolic Blood Pressure (SBP) of > 160 mmHg
  • Resting heart rate of > 100 bpm
  • Significant valvular heart disease
  • Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
  • Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)
  • Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
  • History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course
  • Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
  • Documented room air oxygen saturation reading < 90% at screening
  • Planned septal reduction treatment that cannot be deferred during the trial period
  • History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
  • History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.
  • Current or recent (< 4 weeks) therapy with disopyramide
  • History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
  • Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten

• Participants who meet all the following criteria at screening may be included in the trial:
  • Males and females between 18 to 85 years of age, inclusive, at screening
  • Body mass index < 35 kg/m2
  • Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -
  • Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and
  • Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory:
  • ≥ 15 mm in one or more myocardial segments OR
  • ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM
  • New York Heart Association (NYHA) class II or III
  • Has a Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) score of ≤ 90 at screening
  • Has a screening echocardiogram with the following determined by the echocardiography core laboratory:
  • Resting left ventricular outflow tract gradient (LVOT-G) > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
  • LVEF ≥ 60%
  • Hemoglobin ≥ 10g/dL
  • Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) < 100% predicted on the screening cardiopulmonary exercise testing (CPET) per the core laboratory
  • Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks